Delirium affects up to 80% of mechanically ventilated patients in the intensive care unit (ICU). Delirium duration and severity are independently associated with higher morbidity and mortality. Early identification of patients susceptible to prolonged delirium duration and higher delirium severity will help in instituting effective therapeutic interventions to reduce complications associated with delirium. A personalized approach utilizing biomarkers to identify vulnerable delirious patients prone to increased delirium duration and severity offers promise to curtail the disease burden. This proposal describes a career development plan that will enable Dr. Khan to develop expertise in patient-oriented translational clinical research by acquiring the necessary skills in biomarker technology, bio- informatics and biostatistics. The candidate will study serum biomarkers of inflammation, astrocyte activation and neuroprotection in the context of a large randomized clinical trial, the Pharmacological Management of Delirium (PMD) trial. Dr. Khan's proposed project is a cohort study embedded within the large trial benefiting from the diverse patient population, data acquisition resources, research personnel and other inherent strengths of an R01. The completion of the project will identify a unique set of candidate biomarkers for delirium duration and severity and will establish Dr. Khan as a neurocognitive critical care researcher. The proposed career development plan integrates; a) advanced coursework in molecular biology, biostatistics, and bioinformatics, b) participation in local/national meetings to develop expertise in translational research, c) a multidisciplinary mentored research experience, and d) a highly supportive research environment. This environment includes an internationally recognized NIH funded PMD Study Group, a distinguished Indiana University Center for Aging Research, a renowned Clinical and Translational Sciences Institute, and pioneers in Medical Informatics, the Regenstrief Institute. Overall, this career development award will ensure the necessary protected time required to advance the candidate's career in biomarker based translational critical care research. In addition, the award will provide critical support to guide future translational studies / R01 applications. Future studies will assess the impact of utilizing a personalized approach consisting of early identification of vulnerable delirious patients through serum biomarkers coupled with effective therapeutic interventions in decreasing the morbidity and mortality associated with ICU delirium. PUBLIC HEALTH RELEVANCE: Project Narrative: A significant majority of critically ill patients admitted to the intensive care unit suffers from delirium with both delirium duration and its severity contributing independently to patient's morbidity and mortality. A current role of biomarkers to identify patients prone to prolonged delirium duration and higher severity is uncertain. This project seeks to develop a personalized approach of managing delirium by identifying candidate biomarkers that can prognosticate delirium duration and severity.